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Alternative RNA Splicing

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

Alternative RNA Splicing

Alternative RNA Splicing

RNA Splicing

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

Chromatin Structure Regulates pre-mRNA Processing

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...

Pre-mRNA Processing: RNA Splicing

Pre-mRNA Processing: RNA Splicing

Nonsense-mediated mRNA Decay

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...

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関連する実験動画

Updated: Nov 5, 2025

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

構造化されたRNA要素とのSNRPA1相互作用によって調節されるプロメタスティックスプライシングプログラム

Lisa Fish^1,2,3,4, Matvei Khoroshkin^1,2,3,4, Albertas Navickas^1,2,3,4

¹Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

Science (New York, N.Y.)

|May 14, 2021

まとめ

研究者らは,代替スプライシングを強化することで,癌の転移を促進する新しいRNA構造要素を特定しました. この要素は,乳がん細胞の侵入と肺の植民を誘導する,スプレイスソーマのタンパク質SNRPA1を含みます.

さらに関連する動画

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

Published on: June 30, 2022

関連する実験動画

Last Updated: Nov 5, 2025

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

Published on: June 30, 2022

科学分野:

分子生物学
癌研究
RNA 生物学

背景:

異常な代替スプライシングは癌の重要な特徴ですが,その規制メカニズムは十分に理解されていません.
スプライシングの規制を理解することはターゲットを絞ったがん治療法の開発に不可欠です

研究の目的:

乳がんの転移を制御する RNA 構造コードを調査する.
癌細胞の侵入と転移を制御する新しい規制要因とメカニズムを特定する.

主な方法:

転移性乳がん細胞における代替スプライシングに関連したRNA構造の系統的分析.
スプライシングに関与するタンパク質-RNAの相互作用の識別と特徴付け.
細胞侵入アッセイと in vivo 転移モデルを用いた機能研究
癌の進行における特定のスプライシングイベントの役割を調査する.

主要な成果:

転移細胞に含まれるカセットエクソンの近くで強化された新しい構造スプライシングエンハンサーの発見.
これらの増強剤との主要な相互作用体として,スプライソームタンパク質小核リボ核タンパク質ポリペプチドA' (SNRPA1) の特定.
SNRPA1がカセットエクソンのインクルージョンを促進し,転移性肺のコロニー化と癌細胞の侵入を促進することを示す.
PLECの代替スプライシングのSNRPA1媒介による調節が転移に寄与し,これを調節することができるという証拠.

結論:

SNRPA1は乳がんにおけるプロメテスタティック・スプライシング・エンハンスターとして非正規的な役割を果たしている.
特定されたRNA構造要素とSNRPA1の相互作用は,がん転移における新しい規制軸を表しています.
このSNRPA1媒介のスプライシング経路をターゲットにすると乳がん治療の新たな治療戦略が生まれます